Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan.
Department of Respiratory Medicine, Hannover Medical School and German Centre for Lung Research, Hannover, Germany.
J Am Coll Cardiol. 2018 Feb 20;71(7):752-763. doi: 10.1016/j.jacc.2017.12.010.
Registry data suggest that disease progression in pulmonary arterial hypertension (PAH) is indicative of poor prognosis. However, the prognostic relevance of PAH-related morbidity has not been formally evaluated in randomized controlled trials.
The purpose of these analyses was to assess the impact of morbidity events on the risk of subsequent mortality using the landmark method and data from the SERAPHIN and GRIPHON studies.
For each study, the risk of all-cause death up to the end of the study was assessed from the landmark time point (months 3, 6, and 12) according to whether a patient had experienced a primary endpoint morbidity event before the landmark. Each analysis was conducted using data from all patients who were available for survival follow-up at the landmark.
In the SERAPHIN study, on the basis of the 3-month landmark time point, patients who experienced a morbidity event before month 3 had an increased risk of death compared with patients who did not (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.94 to 5.92). In the GRIPHON study, on the basis of the 3-month landmark time point, there was also an increased risk with a HR of 4.48; (95% CI: 2.98 to 6.73). Analyses based on 6-month and 12-month landmarks also showed increased risk in patients who experienced morbidity events, albeit with a reduced HR.
These results demonstrate the prognostic relevance of PAH-related morbidity as defined in the SERAPHIN and GRIPHON studies, highlighting the importance of preventing disease progression in patients with PAH and supporting the clinical relevance of SERAPHIN and GRIPHON morbidity events. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension [SERAPHIN]; NCT00660179; Selexipag [ACT-293987] in Pulmonary Arterial Hypertension [GRIPHON]; NCT01106014).
注册数据表明，肺动脉高压（PAH）的疾病进展预示着预后不良。然而，在随机对照试验中尚未正式评估 PAH 相关发病率的预后相关性。
本分析旨在使用 landmark 方法和 SERAPHIN 和 GRIPHON 研究的数据评估发病率事件对随后死亡率的风险影响。
对于每项研究，从 landmark 时间点（第 3、6 和 12 个月）评估所有原因死亡的风险，方法是根据患者在 landmark 之前是否经历过主要终点发病率事件。每项分析均使用在 landmark 时具有生存随访的所有患者的数据进行。
在 SERAPHIN 研究中，基于 3 个月的 landmark 时间点，在第 3 个月之前经历发病率事件的患者与未经历发病率事件的患者相比，死亡风险增加（风险比 [HR]：3.39；95%置信区间 [CI]：1.94 至 5.92）。在 GRIPHON 研究中，基于 3 个月的 landmark 时间点，风险也增加，HR 为 4.48（95%CI：2.98 至 6.73）。基于 6 个月和 12 个月 landmark 的分析也显示，经历发病率事件的患者风险增加，尽管 HR 降低。
这些结果表明 SERAPHIN 和 GRIPHON 研究中定义的 PAH 相关发病率具有预后相关性，突出了预防 PAH 患者疾病进展的重要性，并支持 SERAPHIN 和 GRIPHON 发病率事件的临床相关性。（Macitentan [ACT-064992] 在有症状性肺动脉高压患者中的发病率和死亡率研究 [SERAPHIN]；NCT00660179；Selexipag [ACT-293987] 在肺动脉高压中的研究 [GRIPHON]；NCT01106014）。
